A unique immune regulatory system exists in the anterior chamber and has been termed "anterior chamber-associated immune deviation" (ACAID). In ACAID, antigen placed into the anterior chamber is presented to the host immune system in such a way that delayed-type hypersensitivity responses are suppressed. This phenomenon may partly explain the high success rate of corneal transplants, as well as persistent viral infections in the anterior segment. The mechanism of ACAID is unknown as is the location of antigen presentation in the anterior chamber. Cells involved in antigen presentation express Class II surface antigens that are encoded by the Major Histocompatibility Complex. Recently we have demonstrated cells in the human aqueous outflow system that express Class II antigens constitutively. Additional cells in the outflow system can be induced to express Class II antigens by the lymphokine gamma interferon, we speculate that as part of the aqueous outflow system, the trabecular meshwork may be involved in antigen presentation and thereby influence immune responses in the anterior chamber. The goals of the proposed study are to more precisely localize, characterize and evaluate the Class II antigen-bearing cells in the aqueous outflow system and to further explore the relationship between the aqueous outflow channels and the ACAID phenomenon. The location and nature of the positively staining cells in the human aqueous outflow system will be analyzed using immunofluorescence and immunoperoxidase assays. The number of cells will be quantitated and correlated with age. The effect of Class II (Ia) antigen expression on other trabecular cell functions will be explored. Parallel studies will be performed in an inbred mouse model. The aqueous outflow system will be identified with tracer studies. Using indirect immunofluorescence, murine anterior segment tissue will be stained for Ia antigen-bearing cells that are not Langerhans cells. If Ia positive cells are identified, the origin of the cells will be explored by bone marrow chimera studies. An attempt will be made to culture the cells of the outflow system and to study their morphology, growth characteristics and metabolic function in preparation for further immunological assays. Finally, the importance of aqueous drainage to the development of ACAID will be addressed by creating an experimental glaucoma prior to intracameral antigen challenge.